EA020339B1 - Nmda рецепторные антагонисты для лечения нейропсихиатрических расстройств - Google Patents
Nmda рецепторные антагонисты для лечения нейропсихиатрических расстройств Download PDFInfo
- Publication number
- EA020339B1 EA020339B1 EA201071291A EA201071291A EA020339B1 EA 020339 B1 EA020339 B1 EA 020339B1 EA 201071291 A EA201071291 A EA 201071291A EA 201071291 A EA201071291 A EA 201071291A EA 020339 B1 EA020339 B1 EA 020339B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- phenyl
- compound
- piperazin
- alkyl
- hydroxy
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title abstract description 30
- 229940127523 NMDA Receptor Antagonists Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 301
- -1 1-(4-chlorophenyl)-3-(4-hydroxyphenoxy)propyl Chemical group 0.000 claims abstract description 192
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 71
- 238000000034 method Methods 0.000 claims abstract description 71
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 150000002148 esters Chemical class 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 82
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 229910052698 phosphorus Inorganic materials 0.000 claims description 28
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 208000020401 Depressive disease Diseases 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 208000024714 major depressive disease Diseases 0.000 claims description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 239000013256 coordination polymer Substances 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 4
- 239000012634 fragment Substances 0.000 claims description 4
- IRFHMTUHTBSEBK-QGZVFWFLSA-N tert-butyl n-[(2s)-2-(2,5-difluorophenyl)-3-quinolin-3-ylpropyl]carbamate Chemical compound C1([C@H](CC=2C=C3C=CC=CC3=NC=2)CNC(=O)OC(C)(C)C)=CC(F)=CC=C1F IRFHMTUHTBSEBK-QGZVFWFLSA-N 0.000 claims description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 208000019022 Mood disease Diseases 0.000 abstract description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 238000011321 prophylaxis Methods 0.000 abstract 2
- MOVHEMVZXCWLLK-UHFFFAOYSA-N 6-[3-[4-(4-chlorophenyl)piperazin-1-yl]-2-hydroxypropoxy]-1h-quinolin-2-one Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCC(O)CN(CC1)CCN1C1=CC=C(Cl)C=C1 MOVHEMVZXCWLLK-UHFFFAOYSA-N 0.000 abstract 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 72
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 70
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 67
- 238000012360 testing method Methods 0.000 description 66
- 208000035475 disorder Diseases 0.000 description 60
- 230000000694 effects Effects 0.000 description 52
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 51
- 239000000243 solution Substances 0.000 description 43
- 239000004202 carbamide Substances 0.000 description 40
- 239000003814 drug Substances 0.000 description 40
- 102000005962 receptors Human genes 0.000 description 40
- 108020003175 receptors Proteins 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 36
- 239000000203 mixture Substances 0.000 description 36
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 30
- 229940079593 drug Drugs 0.000 description 30
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 210000004556 brain Anatomy 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 21
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 20
- 239000000463 material Substances 0.000 description 20
- 150000002632 lipids Chemical class 0.000 description 19
- 208000019901 Anxiety disease Diseases 0.000 description 18
- 230000036506 anxiety Effects 0.000 description 18
- 239000007787 solid Substances 0.000 description 17
- 241000699670 Mus sp. Species 0.000 description 16
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 15
- 239000005557 antagonist Substances 0.000 description 15
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 229940044551 receptor antagonist Drugs 0.000 description 14
- 239000002464 receptor antagonist Substances 0.000 description 14
- 210000000287 oocyte Anatomy 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 208000020925 Bipolar disease Diseases 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 229930195712 glutamate Natural products 0.000 description 11
- 230000004044 response Effects 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 10
- 230000002996 emotional effect Effects 0.000 description 10
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 10
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 208000006011 Stroke Diseases 0.000 description 9
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 9
- 239000000935 antidepressant agent Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 9
- 108091006146 Channels Proteins 0.000 description 8
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- 125000003342 alkenyl group Chemical group 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 229940005513 antidepressants Drugs 0.000 description 8
- 230000002265 prevention Effects 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 7
- 239000004471 Glycine Substances 0.000 description 7
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 7
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 7
- RTHCYVBBDHJXIQ-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-UHFFFAOYSA-N 0.000 description 7
- 125000002252 acyl group Chemical group 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 208000020016 psychiatric disease Diseases 0.000 description 7
- 230000009182 swimming Effects 0.000 description 7
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 6
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 6
- 208000024827 Alzheimer disease Diseases 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 208000037146 Atypical Timothy syndrome Diseases 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 206010026749 Mania Diseases 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 6
- 230000008485 antagonism Effects 0.000 description 6
- 125000003710 aryl alkyl group Chemical group 0.000 description 6
- 208000037498 atypical type Timothy syndrome Diseases 0.000 description 6
- 125000005605 benzo group Chemical group 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 229960003914 desipramine Drugs 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 6
- 229960002464 fluoxetine Drugs 0.000 description 6
- 150000002391 heterocyclic compounds Chemical class 0.000 description 6
- 238000004896 high resolution mass spectrometry Methods 0.000 description 6
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 201000000980 schizophrenia Diseases 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 231100000331 toxic Toxicity 0.000 description 6
- 230000002588 toxic effect Effects 0.000 description 6
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 5
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 5
- 206010020772 Hypertension Diseases 0.000 description 5
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 5
- 208000018737 Parkinson disease Diseases 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000004379 membrane Anatomy 0.000 description 5
- 206010027175 memory impairment Diseases 0.000 description 5
- 230000037023 motor activity Effects 0.000 description 5
- 229960002296 paroxetine Drugs 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 4
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 4
- XKFPYPQQHFEXRZ-UHFFFAOYSA-N 5-methyl-N'-(phenylmethyl)-3-isoxazolecarbohydrazide Chemical compound O1C(C)=CC(C(=O)NNCC=2C=CC=CC=2)=N1 XKFPYPQQHFEXRZ-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 4
- 208000012902 Nervous system disease Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 208000028017 Psychotic disease Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
- 125000004103 aminoalkyl group Chemical group 0.000 description 4
- 229960000836 amitriptyline Drugs 0.000 description 4
- 230000001430 anti-depressive effect Effects 0.000 description 4
- 230000006399 behavior Effects 0.000 description 4
- 210000005013 brain tissue Anatomy 0.000 description 4
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 4
- 125000004181 carboxyalkyl group Chemical group 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 208000019622 heart disease Diseases 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 230000015654 memory Effects 0.000 description 4
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 4
- BWPIARFWQZKAIA-UHFFFAOYSA-N protriptyline Chemical group C1=CC2=CC=CC=C2C(CCCNC)C2=CC=CC=C21 BWPIARFWQZKAIA-UHFFFAOYSA-N 0.000 description 4
- 229940035613 prozac Drugs 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 3
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 3
- UUDAMDVQRQNNHZ-UHFFFAOYSA-N (S)-AMPA Chemical compound CC=1ONC(=O)C=1CC(N)C(O)=O UUDAMDVQRQNNHZ-UHFFFAOYSA-N 0.000 description 3
- XLHUBROMZOAQMV-UHFFFAOYSA-N 1,4-benzosemiquinone Chemical group [O]C1=CC=C(O)C=C1 XLHUBROMZOAQMV-UHFFFAOYSA-N 0.000 description 3
- VRVIKRZIQWEYFB-UHFFFAOYSA-N 1-(3,4-difluorophenyl)piperazine Chemical compound C1=C(F)C(F)=CC=C1N1CCNCC1 VRVIKRZIQWEYFB-UHFFFAOYSA-N 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- 101100027896 Arabidopsis thaliana OCP3 gene Proteins 0.000 description 3
- 208000000412 Avitaminosis Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 208000003174 Brain Neoplasms Diseases 0.000 description 3
- 208000017667 Chronic Disease Diseases 0.000 description 3
- 208000028698 Cognitive impairment Diseases 0.000 description 3
- 206010054089 Depressive symptom Diseases 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 206010015535 Euphoric mood Diseases 0.000 description 3
- 102000018899 Glutamate Receptors Human genes 0.000 description 3
- 108010027915 Glutamate Receptors Proteins 0.000 description 3
- 208000004547 Hallucinations Diseases 0.000 description 3
- 206010021135 Hypovitaminosis Diseases 0.000 description 3
- 101100521345 Mus musculus Prop1 gene Proteins 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 206010033664 Panic attack Diseases 0.000 description 3
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 108700017836 Prophet of Pit-1 Proteins 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- BKPRVQDIOGQWTG-ICOOEGOYSA-N [(1s,2r)-2-phenylcyclopropyl]azanium;[(1r,2s)-2-phenylcyclopropyl]azanium;sulfate Chemical compound [O-]S([O-])(=O)=O.[NH3+][C@H]1C[C@@H]1C1=CC=CC=C1.[NH3+][C@@H]1C[C@H]1C1=CC=CC=C1 BKPRVQDIOGQWTG-ICOOEGOYSA-N 0.000 description 3
- 230000009102 absorption Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 125000003368 amide group Chemical group 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 229940009098 aspartate Drugs 0.000 description 3
- 229960004754 astemizole Drugs 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000008499 blood brain barrier function Effects 0.000 description 3
- 229960001058 bupropion Drugs 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000007541 cellular toxicity Effects 0.000 description 3
- 229960001653 citalopram Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 208000010877 cognitive disease Diseases 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 229960004341 escitalopram Drugs 0.000 description 3
- WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 208000006454 hepatitis Diseases 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229960004801 imipramine Drugs 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 201000004792 malaria Diseases 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 3
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 3
- 229960001158 nortriptyline Drugs 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- 208000019906 panic disease Diseases 0.000 description 3
- UNEIHNMKASENIG-UHFFFAOYSA-N para-chlorophenylpiperazine Chemical compound C1=CC(Cl)=CC=C1N1CCNCC1 UNEIHNMKASENIG-UHFFFAOYSA-N 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229960003975 potassium Drugs 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229940100992 sarafem Drugs 0.000 description 3
- 208000012672 seasonal affective disease Diseases 0.000 description 3
- 230000001932 seasonal effect Effects 0.000 description 3
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000008279 sol Substances 0.000 description 3
- 238000004611 spectroscopical analysis Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 3
- PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 description 3
- ZSCDBOWYZJWBIY-UHFFFAOYSA-N trimipramine Chemical group C1CC2=CC=CC=C2N(CC(CN(C)C)C)C2=CC=CC=C21 ZSCDBOWYZJWBIY-UHFFFAOYSA-N 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 208000030401 vitamin deficiency disease Diseases 0.000 description 3
- KTGRHKOEFSJQNS-BDQAORGHSA-N (1s)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3h-2-benzofuran-5-carbonitrile;oxalic acid Chemical compound OC(=O)C(O)=O.C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 KTGRHKOEFSJQNS-BDQAORGHSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 2
- AKEMIRQFANFFKU-NCYRAAIKSA-N 2-[[(2s,4as,6ar,6as,6br,8ar,10s,12as)-10-(2-carboxybenzoyl)oxy-2,4a,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12-dodecahydropicen-2-yl]methoxycarbonyl]benzoic acid Chemical compound C([C@]1(C)CC2=C3[C@@]([C@@]4(CC[C@H]5C(C)(C)[C@@H](OC(=O)C=6C(=CC=CC=6)C(O)=O)CC[C@]5(C)[C@H]4C=C3)C)(C)CC[C@@]2(C)CC1)OC(=O)C1=CC=CC=C1C(O)=O AKEMIRQFANFFKU-NCYRAAIKSA-N 0.000 description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 238000010953 Ames test Methods 0.000 description 2
- 231100000039 Ames test Toxicity 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 206010012218 Delirium Diseases 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- LFMYNZPAVPMEGP-PIDGMYBPSA-N Fluvoxamine maleate Chemical compound OC(=O)\C=C/C(O)=O.COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 LFMYNZPAVPMEGP-PIDGMYBPSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 102100021337 Gap junction alpha-1 protein Human genes 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000894966 Homo sapiens Gap junction alpha-1 protein Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 102000004310 Ion Channels Human genes 0.000 description 2
- 108090000862 Ion Channels Proteins 0.000 description 2
- VLSMHEGGTFMBBZ-OOZYFLPDSA-M Kainate Chemical compound CC(=C)[C@H]1C[NH2+][C@H](C([O-])=O)[C@H]1CC([O-])=O VLSMHEGGTFMBBZ-OOZYFLPDSA-M 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 206010033864 Paranoia Diseases 0.000 description 2
- 208000027099 Paranoid disease Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- RMUCZJUITONUFY-UHFFFAOYSA-N Phenelzine Chemical compound NNCCC1=CC=CC=C1 RMUCZJUITONUFY-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 102000004257 Potassium Channel Human genes 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000010513 Stupor Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 101150033985 TPI gene Proteins 0.000 description 2
- 101150032817 TPI1 gene Proteins 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 108700015934 Triose-phosphate isomerases Proteins 0.000 description 2
- 102100033598 Triosephosphate isomerase Human genes 0.000 description 2
- 241001136075 Trulla Species 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- OCYPZIZIRIFBMY-UHFFFAOYSA-N [4-[3-[4-(3,4-difluorophenyl)piperazin-1-yl]propoxy]phenyl]urea Chemical compound C1=CC(NC(=O)N)=CC=C1OCCCN1CCN(C=2C=C(F)C(F)=CC=2)CC1 OCYPZIZIRIFBMY-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000005041 acyloxyalkyl group Chemical group 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
- 102000030619 alpha-1 Adrenergic Receptor Human genes 0.000 description 2
- 108020004102 alpha-1 Adrenergic Receptor Proteins 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 2
- 229960003805 amantadine Drugs 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000008503 anti depressant like effect Effects 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 230000001174 ascending effect Effects 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 208000026725 cyclothymic disease Diseases 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000000221 dopamine uptake inhibitor Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 229960005426 doxepin Drugs 0.000 description 2
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 2
- 238000002635 electroconvulsive therapy Methods 0.000 description 2
- 239000003974 emollient agent Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 230000002743 euphoric effect Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 230000002964 excitative effect Effects 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 125000001207 fluorophenyl group Chemical group 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 231100000025 genetic toxicology Toxicity 0.000 description 2
- 230000001738 genotoxic effect Effects 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000009931 harmful effect Effects 0.000 description 2
- 150000002390 heteroarenes Chemical class 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 229960002672 isocarboxazid Drugs 0.000 description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229940054157 lexapro Drugs 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 238000011866 long-term treatment Methods 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229960004090 maprotiline Drugs 0.000 description 2
- QSLMDECMDJKHMQ-GSXCWMCISA-N maprotiline Chemical compound C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 description 2
- 229940110127 marplan Drugs 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 2
- 229960004640 memantine Drugs 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 230000003228 microsomal effect Effects 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 2
- 238000002552 multiple reaction monitoring Methods 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 230000036963 noncompetitive effect Effects 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- 229940127221 norepinephrine reuptake inhibitor Drugs 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
- 150000002924 oxiranes Chemical class 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 229940087824 parnate Drugs 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 108020001213 potassium channel Proteins 0.000 description 2
- 229960001289 prazosin Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000003825 pressing Methods 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 229960002601 protriptyline Drugs 0.000 description 2
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- 229940081974 saccharin Drugs 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 229960002073 sertraline Drugs 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 239000012134 supernatant fraction Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229940127228 tetracyclic antidepressant Drugs 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- 229920006259 thermoplastic polyimide Polymers 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 229940041597 tofranil Drugs 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 229960003991 trazodone Drugs 0.000 description 2
- 229960002431 trimipramine Drugs 0.000 description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 2
- 229940020965 zoloft Drugs 0.000 description 2
- CVTFNNJUXOBPMI-UHFFFAOYSA-N (1,2-dichloro-2-diphenylphosphanylethyl)-diphenylphosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(Cl)C(Cl)P(C=1C=CC=CC=1)C1=CC=CC=C1 CVTFNNJUXOBPMI-UHFFFAOYSA-N 0.000 description 1
- IGLYMJRIWWIQQE-QUOODJBBSA-N (1S,2R)-2-phenylcyclopropan-1-amine (1R,2S)-2-phenylcyclopropan-1-amine Chemical compound N[C@H]1C[C@@H]1C1=CC=CC=C1.N[C@@H]1C[C@H]1C1=CC=CC=C1 IGLYMJRIWWIQQE-QUOODJBBSA-N 0.000 description 1
- XOYSDPUJMJWCBH-VKHMYHEASA-N (3s)-3,5-diamino-5-oxopentanoic acid Chemical compound NC(=O)C[C@H](N)CC(O)=O XOYSDPUJMJWCBH-VKHMYHEASA-N 0.000 description 1
- SHIJTGJXUHTGGZ-RVXRQPKJSA-N (3s,4r)-3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidin-1-ium;methanesulfonate Chemical compound CS(O)(=O)=O.C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 SHIJTGJXUHTGGZ-RVXRQPKJSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical class C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- UPPYOQWUJKAFSG-UHFFFAOYSA-N 1,3-benzoxazol-5-ol Chemical compound OC1=CC=C2OC=NC2=C1 UPPYOQWUJKAFSG-UHFFFAOYSA-N 0.000 description 1
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- JIWHIRLNKIUYSM-UHFFFAOYSA-N 1-(3-methylphenyl)piperazine Chemical compound CC1=CC=CC(N2CCNCC2)=C1 JIWHIRLNKIUYSM-UHFFFAOYSA-N 0.000 description 1
- NBOUJFMSFIQBQF-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[2-hydroxy-3-(4-hydroxyphenoxy)propyl]imidazolidin-2-one Chemical compound C1CN(C=2C=CC(Cl)=CC=2)C(=O)N1CC(O)COC1=CC=C(O)C=C1 NBOUJFMSFIQBQF-UHFFFAOYSA-N 0.000 description 1
- CRFOCNNSZAEXLS-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[3-(4-hydroxyphenoxy)propyl]imidazolidin-2-one Chemical compound C1=CC(O)=CC=C1OCCCN1C(=O)N(C=2C=CC(Cl)=CC=2)CC1 CRFOCNNSZAEXLS-UHFFFAOYSA-N 0.000 description 1
- AVJKDKWRVSSJPK-UHFFFAOYSA-N 1-(4-fluorophenyl)piperazine Chemical compound C1=CC(F)=CC=C1N1CCNCC1 AVJKDKWRVSSJPK-UHFFFAOYSA-N 0.000 description 1
- DMEHPDNBUYEJGP-UHFFFAOYSA-N 1-(4-propan-2-ylphenyl)piperazine Chemical compound C1=CC(C(C)C)=CC=C1N1CCNCC1 DMEHPDNBUYEJGP-UHFFFAOYSA-N 0.000 description 1
- IFSPIWXCVCISKM-UHFFFAOYSA-N 1-(4-propylphenyl)piperazine Chemical compound C1=CC(CCC)=CC=C1N1CCNCC1 IFSPIWXCVCISKM-UHFFFAOYSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- WEAYCYAIVOIUMG-UHFFFAOYSA-N 1-methyl-4-(4-methylphenyl)sulfonylbenzene Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C1=CC=C(C)C=C1 WEAYCYAIVOIUMG-UHFFFAOYSA-N 0.000 description 1
- BBYWOYAFBUOUFP-JOCHJYFZSA-N 1-stearoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)COP(O)(=O)OCCN BBYWOYAFBUOUFP-JOCHJYFZSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- VFTFKUDGYRBSAL-UHFFFAOYSA-N 15-crown-5 Chemical compound C1COCCOCCOCCOCCO1 VFTFKUDGYRBSAL-UHFFFAOYSA-N 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- PYHXGXCGESYPCW-UHFFFAOYSA-M 2,2-diphenylacetate Chemical compound C=1C=CC=CC=1C(C(=O)[O-])C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-M 0.000 description 1
- OJHWPOJTJKJBLA-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-benzimidazole Chemical compound C1C=CC=C2NCNC21 OJHWPOJTJKJBLA-UHFFFAOYSA-N 0.000 description 1
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- ZDHWTWWXCXEGIC-UHFFFAOYSA-N 2-ethenylpyrimidine Chemical compound C=CC1=NC=CC=N1 ZDHWTWWXCXEGIC-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- KONALDCHZKKWOY-UHFFFAOYSA-N 2-propoxybenzene-1,3-diol Chemical compound CCCOC1=C(O)C=CC=C1O KONALDCHZKKWOY-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- PKVXOQIKRLHBPM-UHFFFAOYSA-N 3-[4-(methanesulfonamido)phenyl]propanoic acid Chemical compound CS(=O)(=O)NC1=CC=C(CCC(O)=O)C=C1 PKVXOQIKRLHBPM-UHFFFAOYSA-N 0.000 description 1
- HCKUBNLZMKAEIN-UHFFFAOYSA-N 3-amino-1-hydroxypyrrolidin-2-one Chemical compound NC1CCN(O)C1=O HCKUBNLZMKAEIN-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- YHQXBTXEYZIYOV-UHFFFAOYSA-N 3-methylbut-1-ene Chemical compound CC(C)C=C YHQXBTXEYZIYOV-UHFFFAOYSA-N 0.000 description 1
- VYIBCOSBNVFEIW-UHFFFAOYSA-N 3-phenylpropanamide Chemical compound NC(=O)CCC1=CC=CC=C1 VYIBCOSBNVFEIW-UHFFFAOYSA-N 0.000 description 1
- UYNVMODNBIQBMV-UHFFFAOYSA-N 4-[1-hydroxy-2-[4-(phenylmethyl)-1-piperidinyl]propyl]phenol Chemical compound C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1 UYNVMODNBIQBMV-UHFFFAOYSA-N 0.000 description 1
- KZTVHIZALLBXMO-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxyphenol Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=C(O)C=C1 KZTVHIZALLBXMO-UHFFFAOYSA-N 0.000 description 1
- WXOHKMNWMKZMND-UHFFFAOYSA-N 4-aminohydrocinnamic acid Chemical compound NC1=CC=C(CCC(O)=O)C=C1 WXOHKMNWMKZMND-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 description 1
- WDEOVTRPWGBRPF-QFIPXVFZSA-N 5-[(2s)-3-[4-(4-butylphenyl)piperazin-1-yl]-2-hydroxypropoxy]-1,3-dihydroindol-2-one Chemical compound C1=CC(CCCC)=CC=C1N1CCN(C[C@H](O)COC=2C=C3CC(=O)NC3=CC=2)CC1 WDEOVTRPWGBRPF-QFIPXVFZSA-N 0.000 description 1
- GQDDIWJTESLCNB-UHFFFAOYSA-N 5-[2-[4-(3,4-difluorophenyl)piperazin-1-yl]-2-oxoethoxy]-1,3-dihydroindol-2-one Chemical compound C1=C(F)C(F)=CC=C1N1CCN(C(=O)COC=2C=C3CC(=O)NC3=CC=2)CC1 GQDDIWJTESLCNB-UHFFFAOYSA-N 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
- KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 description 1
- ORQCZGJBTQRSGI-QFIPXVFZSA-N 6-[(2s)-3-[4-(4-cyclopropylphenyl)piperazin-1-yl]-2-hydroxypropoxy]-1h-quinolin-2-one Chemical compound C([C@@H](COC=1C=C2C=CC(=O)NC2=CC=1)O)N(CC1)CCN1C(C=C1)=CC=C1C1CC1 ORQCZGJBTQRSGI-QFIPXVFZSA-N 0.000 description 1
- JOWHVLCQGOYQOV-UHFFFAOYSA-N 6-[2-[4-(3,4-dichlorophenyl)piperazin-1-yl]-2-oxoethoxy]-1h-quinolin-2-one Chemical compound C1=C(Cl)C(Cl)=CC=C1N1CCN(C(=O)COC=2C=C3C=CC(=O)NC3=CC=2)CC1 JOWHVLCQGOYQOV-UHFFFAOYSA-N 0.000 description 1
- RFYQXHHAYAEDRR-UHFFFAOYSA-N 6-[2-[4-(3,4-dichlorophenyl)piperazin-1-yl]-2-oxoethoxy]-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=C(Cl)C(Cl)=CC=C1N1CCN(C(=O)COC=2C=C3CCC(=O)NC3=CC=2)CC1 RFYQXHHAYAEDRR-UHFFFAOYSA-N 0.000 description 1
- PIKJQCMEAGPQHT-UHFFFAOYSA-N 6-[2-[4-(3,4-difluorophenyl)piperazin-1-yl]-2-oxoethoxy]-1h-quinolin-2-one Chemical compound C1=C(F)C(F)=CC=C1N1CCN(C(=O)COC=2C=C3C=CC(=O)NC3=CC=2)CC1 PIKJQCMEAGPQHT-UHFFFAOYSA-N 0.000 description 1
- PTXZHWMPYVIFFN-UHFFFAOYSA-N 6-[2-[4-(3,4-difluorophenyl)piperazin-1-yl]-2-oxoethoxy]-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=C(F)C(F)=CC=C1N1CCN(C(=O)COC=2C=C3CCC(=O)NC3=CC=2)CC1 PTXZHWMPYVIFFN-UHFFFAOYSA-N 0.000 description 1
- YRXJMRDDUXIMTR-UHFFFAOYSA-N 6-[2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethoxy]-1h-quinolin-2-one Chemical compound C1=CC(Cl)=CC=C1N1CCN(C(=O)COC=2C=C3C=CC(=O)NC3=CC=2)CC1 YRXJMRDDUXIMTR-UHFFFAOYSA-N 0.000 description 1
- PEMSIQHHRCXXHQ-UHFFFAOYSA-N 6-[2-hydroxy-3-[4-(4-propan-2-ylphenyl)piperazin-1-yl]propoxy]-1h-quinolin-2-one Chemical compound C1=CC(C(C)C)=CC=C1N1CCN(CC(O)COC=2C=C3C=CC(=O)NC3=CC=2)CC1 PEMSIQHHRCXXHQ-UHFFFAOYSA-N 0.000 description 1
- XPNXKMLSLHJFIP-UHFFFAOYSA-N 6-[3-[4-(4-butylphenyl)piperazin-1-yl]-2-hydroxypropoxy]-1h-quinolin-2-one Chemical compound C1=CC(CCCC)=CC=C1N1CCN(CC(O)COC=2C=C3C=CC(=O)NC3=CC=2)CC1 XPNXKMLSLHJFIP-UHFFFAOYSA-N 0.000 description 1
- PPQAYTVSNWXJPN-UHFFFAOYSA-N 6-[3-[4-(4-chlorophenyl)piperazin-1-yl]-3-oxopropoxy]-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC(Cl)=CC=C1N1CCN(C(=O)CCOC=2C=C3CCC(=O)NC3=CC=2)CC1 PPQAYTVSNWXJPN-UHFFFAOYSA-N 0.000 description 1
- PVRBGBGMDLPYKG-UHFFFAOYSA-N 6-benzyl-7h-purine Chemical compound N=1C=NC=2N=CNC=2C=1CC1=CC=CC=C1 PVRBGBGMDLPYKG-UHFFFAOYSA-N 0.000 description 1
- BUCORZSTKDOEKQ-UHFFFAOYSA-N 7-chloro-4-hydroxy-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-imine Chemical compound C=12C=C(Cl)C=CC2=NC(=NC)CN(O)C=1C1=CC=CC=C1 BUCORZSTKDOEKQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102100026041 Acrosin Human genes 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 101001008613 Arthrobacter globiformis Ketose 3-epimerase Proteins 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282421 Canidae Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 229940094659 Dopamine reuptake inhibitor Drugs 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241001539473 Euphoria Species 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 229940122459 Glutamate antagonist Drugs 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 101100108040 Homo sapiens ACR gene Proteins 0.000 description 1
- 101000897480 Homo sapiens C-C motif chemokine 2 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 102000000079 Kainic Acid Receptors Human genes 0.000 description 1
- 108010069902 Kainic Acid Receptors Proteins 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- NZDMFGKECODQRY-UHFFFAOYSA-N Maprotiline hydrochloride Chemical compound Cl.C12=CC=CC=C2C2(CCCNC)C3=CC=CC=C3C1CC2 NZDMFGKECODQRY-UHFFFAOYSA-N 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 206010027940 Mood altered Diseases 0.000 description 1
- 208000019430 Motor disease Diseases 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 101710138657 Neurotoxin Proteins 0.000 description 1
- 241000849798 Nita Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- RGCVKNLCSQQDEP-UHFFFAOYSA-N Perphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 RGCVKNLCSQQDEP-UHFFFAOYSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- RXBKMJIPNDOHFR-UHFFFAOYSA-N Phenelzine sulfate Chemical compound OS(O)(=O)=O.NNCCC1=CC=CC=C1 RXBKMJIPNDOHFR-UHFFFAOYSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 229940121991 Serotonin and norepinephrine reuptake inhibitor Drugs 0.000 description 1
- 102100037580 Sesquipedalian-1 Human genes 0.000 description 1
- 101710169844 Sesquipedalian-1 Proteins 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 231100000288 TD50 Toxicity 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 241000656145 Thyrsites atun Species 0.000 description 1
- 241001325280 Tricardia watsonii Species 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 208000009729 Ventricular Premature Complexes Diseases 0.000 description 1
- DRUXBXRBEZXWNM-QFIPXVFZSA-N [4-[(2s)-2-hydroxy-3-(4-naphthalen-2-ylpiperazin-1-yl)propoxy]phenyl]urea Chemical compound C1=CC(NC(=O)N)=CC=C1OC[C@@H](O)CN1CCN(C=2C=C3C=CC=CC3=CC=2)CC1 DRUXBXRBEZXWNM-QFIPXVFZSA-N 0.000 description 1
- UUDMANLVAQREMK-QFIPXVFZSA-N [4-[(2s)-2-hydroxy-3-[4-[4-(2-methylpropyl)phenyl]piperazin-1-yl]propoxy]phenyl]urea Chemical compound C1=CC(CC(C)C)=CC=C1N1CCN(C[C@H](O)COC=2C=CC(NC(N)=O)=CC=2)CC1 UUDMANLVAQREMK-QFIPXVFZSA-N 0.000 description 1
- VYXZZIIYJGMYDF-UHFFFAOYSA-N [4-[2-hydroxy-3-[4-(4-propan-2-ylphenyl)piperazin-1-yl]propoxy]phenyl]urea Chemical compound C1=CC(C(C)C)=CC=C1N1CCN(CC(O)COC=2C=CC(NC(N)=O)=CC=2)CC1 VYXZZIIYJGMYDF-UHFFFAOYSA-N 0.000 description 1
- IZSHRHBFWKIGHT-UHFFFAOYSA-N [4-[2-hydroxy-3-[4-(4-propylphenyl)piperazin-1-yl]propoxy]phenyl]urea Chemical compound C1=CC(CCC)=CC=C1N1CCN(CC(O)COC=2C=CC(NC(N)=O)=CC=2)CC1 IZSHRHBFWKIGHT-UHFFFAOYSA-N 0.000 description 1
- KWXGEUXJQVRHGK-UHFFFAOYSA-N [4-[3-[4-(4-ethylphenyl)piperazin-1-yl]-2-hydroxypropoxy]phenyl]urea Chemical compound C1=CC(CC)=CC=C1N1CCN(CC(O)COC=2C=CC(NC(N)=O)=CC=2)CC1 KWXGEUXJQVRHGK-UHFFFAOYSA-N 0.000 description 1
- HBJVEYKZOJRUPW-UHFFFAOYSA-N [4-[3-[4-(4-fluorophenyl)piperazin-1-yl]propoxy]phenyl]urea Chemical compound C1=CC(NC(=O)N)=CC=C1OCCCN1CCN(C=2C=CC(F)=CC=2)CC1 HBJVEYKZOJRUPW-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003194 amino acid receptor blocking agent Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229960002519 amoxapine Drugs 0.000 description 1
- QWGDMFLQWFTERH-UHFFFAOYSA-N amoxapine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2N=C1N1CCNCC1 QWGDMFLQWFTERH-UHFFFAOYSA-N 0.000 description 1
- 229940025141 anafranil Drugs 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- YCSBALJAGZKWFF-UHFFFAOYSA-N anthracen-2-amine Chemical compound C1=CC=CC2=CC3=CC(N)=CC=C3C=C21 YCSBALJAGZKWFF-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 229940092738 beeswax Drugs 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 238000011953 bioanalysis Methods 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- QIHLUZAFSSMXHQ-UHFFFAOYSA-N budipine Chemical compound C1CN(C(C)(C)C)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 QIHLUZAFSSMXHQ-UHFFFAOYSA-N 0.000 description 1
- 229960002452 budipine Drugs 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000002371 cardiac agent Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000003654 cell permeability assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical compound C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229960004782 chlordiazepoxide Drugs 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229960004606 clomipramine Drugs 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 235000013409 condiments Nutrition 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229960003077 cycloserine Drugs 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- YKZPPPNXRZHVGX-PXYKVGKMSA-L dipotassium;(2s)-2-aminobutanedioate;hydron;hydrate Chemical compound [H+].[H+].O.[K+].[K+].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O YKZPPPNXRZHVGX-PXYKVGKMSA-L 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- QLTXKCWMEZIHBJ-PJGJYSAQSA-N dizocilpine maleate Chemical compound OC(=O)\C=C/C(O)=O.C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 QLTXKCWMEZIHBJ-PJGJYSAQSA-N 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 229940112141 dry powder inhaler Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229960002866 duloxetine Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 229940098766 effexor Drugs 0.000 description 1
- 229940011681 elavil Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 125000002534 ethynyl group Chemical class [H]C#C* 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229960002107 fluvoxamine maleate Drugs 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 229960003998 ifenprodil Drugs 0.000 description 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910001867 inorganic solvent Inorganic materials 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 238000003046 intermediate neglect of differential overlap Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- NIZHERJWXFHGGU-UHFFFAOYSA-N isocyanato(trimethyl)silane Chemical compound C[Si](C)(C)N=C=O NIZHERJWXFHGGU-UHFFFAOYSA-N 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 229910052745 lead Inorganic materials 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- CHFSOFHQIZKQCR-UHFFFAOYSA-N licostinel Chemical compound N1C(=O)C(=O)NC2=C1C=C(Cl)C(Cl)=C2[N+](=O)[O-] CHFSOFHQIZKQCR-UHFFFAOYSA-N 0.000 description 1
- 229940087372 limbitrol Drugs 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 230000007787 long-term memory Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 208000012866 low blood pressure Diseases 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229940009622 luvox Drugs 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 102000006239 metabotropic receptors Human genes 0.000 description 1
- 108020004083 metabotropic receptors Proteins 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- LXHNQRGWWMORLQ-UHFFFAOYSA-N methyl 3-(4-aminophenyl)propanoate Chemical compound COC(=O)CCC1=CC=C(N)C=C1 LXHNQRGWWMORLQ-UHFFFAOYSA-N 0.000 description 1
- METRPGNMBXFJST-UHFFFAOYSA-N methyl 3-[4-(methanesulfonamido)phenyl]propanoate Chemical compound COC(=O)CCC1=CC=C(NS(C)(=O)=O)C=C1 METRPGNMBXFJST-UHFFFAOYSA-N 0.000 description 1
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229960001785 mirtazapine Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 230000007510 mood change Effects 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- SGNSAMGUMVFALJ-UHFFFAOYSA-N n,n'-dichloroethane-1,2-diamine Chemical compound ClNCCNCl SGNSAMGUMVFALJ-UHFFFAOYSA-N 0.000 description 1
- ZPUFUUFLTKLBOV-UHFFFAOYSA-N n-(4-hydroxyphenyl)pentanamide Chemical compound CCCCC(=O)NC1=CC=C(O)C=C1 ZPUFUUFLTKLBOV-UHFFFAOYSA-N 0.000 description 1
- ZODXHEFTTJWNPK-UHFFFAOYSA-N n-[4-[2-[2-(3,4-dichloroanilino)ethylamino]ethoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OCCNCCNC1=CC=C(Cl)C(Cl)=C1 ZODXHEFTTJWNPK-UHFFFAOYSA-N 0.000 description 1
- QQKFLUBSTABOJV-UHFFFAOYSA-N n-[4-[3-[2-(3,4-dichloroanilino)ethylamino]propyl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1CCCNCCNC1=CC=C(Cl)C(Cl)=C1 QQKFLUBSTABOJV-UHFFFAOYSA-N 0.000 description 1
- APXVOEZTGMASLV-UHFFFAOYSA-N n-[4-[3-[3-(3,4-dichlorophenyl)-2-oxoimidazolidin-1-yl]propyl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1CCCN1C(=O)N(C=2C=C(Cl)C(Cl)=CC=2)CC1 APXVOEZTGMASLV-UHFFFAOYSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229940087524 nardil Drugs 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000007383 nerve stimulation Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- LBQAJLBSGOBDQF-UHFFFAOYSA-N nitro azanylidynemethanesulfonate Chemical compound [O-][N+](=O)OS(=O)(=O)C#N LBQAJLBSGOBDQF-UHFFFAOYSA-N 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 1
- 229960005017 olanzapine Drugs 0.000 description 1
- 238000012346 open field test Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229940055692 pamelor Drugs 0.000 description 1
- 229960002567 paroxetine mesylate Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229950010883 phencyclidine Drugs 0.000 description 1
- 229960000964 phenelzine Drugs 0.000 description 1
- 229960004790 phenelzine sulfate Drugs 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 125000005499 phosphonyl group Chemical group 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 235000021395 porridge Nutrition 0.000 description 1
- 229940068988 potassium aspartate Drugs 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000004800 psychological effect Effects 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- HBCQSNAFLVXVAY-UHFFFAOYSA-N pyrimidine-2-thiol Chemical compound SC1=NC=CC=N1 HBCQSNAFLVXVAY-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000003087 receptor blocking agent Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229940023942 remeron Drugs 0.000 description 1
- 230000002336 repolarization Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 102220082846 rs373113507 Human genes 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000000698 schizophrenic effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 230000006403 short-term memory Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000008925 spontaneous activity Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 201000009032 substance abuse Diseases 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000004354 sulfur functional group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229940118176 surmontil Drugs 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- AWLILQARPMWUHA-UHFFFAOYSA-M thiopental sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC([S-])=NC1=O AWLILQARPMWUHA-UHFFFAOYSA-M 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 229940035276 tofranil-pm Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000008009 topical excipient Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 238000011491 transcranial magnetic stimulation Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229960003741 tranylcypromine Drugs 0.000 description 1
- 229960003797 tranylcypromine sulfate Drugs 0.000 description 1
- OVCXRBARSPBVMC-UHFFFAOYSA-N triazolopyridine Chemical compound C=1N2C(C(C)C)=NN=C2C=CC=1C=1OC=NC=1C1=CC=C(F)C=C1 OVCXRBARSPBVMC-UHFFFAOYSA-N 0.000 description 1
- ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YDGHCKHAXOUQOS-BTJKTKAUSA-N trimipramine maleate Chemical compound [O-]C(=O)\C=C/C([O-])=O.C1CC2=CC=CC=C2[NH+](CC(C[NH+](C)C)C)C2=CC=CC=C21 YDGHCKHAXOUQOS-BTJKTKAUSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229960004688 venlafaxine Drugs 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- MJIBOYFUEIDNPI-HBNMXAOGSA-L zinc 5-[2,3-dihydroxy-5-[(2R,3R,4S,5R,6S)-4,5,6-tris[[3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoyl]oxy]-2-[[3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoyl]oxymethyl]oxan-3-yl]oxycarbonylphenoxy]carbonyl-3-hydroxybenzene-1,2-diolate Chemical compound [Zn++].Oc1cc(cc(O)c1O)C(=O)Oc1cc(cc(O)c1O)C(=O)OC[C@H]1O[C@@H](OC(=O)c2cc(O)c(O)c(OC(=O)c3cc(O)c(O)c(O)c3)c2)[C@H](OC(=O)c2cc(O)c(O)c(OC(=O)c3cc(O)c(O)c(O)c3)c2)[C@@H](OC(=O)c2cc(O)c(O)c(OC(=O)c3cc(O)c(O)c(O)c3)c2)[C@@H]1OC(=O)c1cc(O)c(O)c(OC(=O)c2cc(O)c([O-])c([O-])c2)c1 MJIBOYFUEIDNPI-HBNMXAOGSA-L 0.000 description 1
- 229940018503 zyban Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4465—Non condensed piperidines, e.g. piperocaine only substituted in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12709808P | 2008-05-09 | 2008-05-09 | |
PCT/US2009/043502 WO2009137843A2 (en) | 2008-05-09 | 2009-05-11 | Nmda receptor antagonists for the treatment of neuropsychiatric disorders |
Publications (3)
Publication Number | Publication Date |
---|---|
EA201071291A2 EA201071291A2 (ru) | 2011-04-29 |
EA201071291A3 EA201071291A3 (ru) | 2014-02-28 |
EA020339B1 true EA020339B1 (ru) | 2014-10-30 |
Family
ID=41265475
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EA201071291A EA020339B1 (ru) | 2008-05-09 | 2009-05-11 | Nmda рецепторные антагонисты для лечения нейропсихиатрических расстройств |
Country Status (16)
Country | Link |
---|---|
US (1) | US20110160223A1 (de) |
EP (1) | EP2296658A4 (de) |
JP (1) | JP2011520815A (de) |
KR (1) | KR20110016891A (de) |
CN (1) | CN102762207A (de) |
AU (1) | AU2009244082A1 (de) |
BR (1) | BRPI0912362A2 (de) |
CA (1) | CA2722776A1 (de) |
CO (1) | CO6341558A2 (de) |
EA (1) | EA020339B1 (de) |
IL (1) | IL208895A0 (de) |
MX (1) | MX2010012186A (de) |
NZ (1) | NZ589764A (de) |
SG (1) | SG195568A1 (de) |
WO (1) | WO2009137843A2 (de) |
ZA (1) | ZA201007958B (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11865088B2 (en) | 2018-10-05 | 2024-01-09 | Clexio Biosciences Ltd. | Method of treating major depressive disorder |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MX2012008721A (es) | 2010-02-16 | 2012-08-17 | Pfizer | (r)-4-((4-((4-(tetrahidrofuran-3-iloxi)benzo[d]isoxazol-3-iloxi)m etil) tetrahidro-2h-piran-4-ol, un agonista pacial de receptores 5-ht4. |
CN113956315A (zh) | 2011-09-08 | 2022-01-21 | 萨奇治疗股份有限公司 | 神经活性类固醇、组合物、及其用途 |
WO2013170072A2 (en) * | 2012-05-09 | 2013-11-14 | Neurop, Inc. | Compounds for the treatment of neurological disorders |
CA2872883A1 (en) * | 2012-05-09 | 2013-11-14 | Sunovion Pharmaceuticals Inc. | Heteroaryl compounds and methods of use thereof |
US8974365B2 (en) * | 2012-11-25 | 2015-03-10 | Steven Richard Devore Best | Treatment of thalamocortical dysrhythmia |
ES2886506T3 (es) | 2013-03-13 | 2021-12-20 | Sage Therapeutics Inc | Esteroides neuroactivos |
WO2014210456A1 (en) | 2013-06-28 | 2014-12-31 | Emory University | Pyrazoline dihydroquinolones, pharmaceutical compositions, and uses |
EP4306114A1 (de) | 2014-06-18 | 2024-01-17 | Sage Therapeutics, Inc. | Oxysterole und verfahren zu ihrer verwendung |
MX2017004684A (es) * | 2014-10-07 | 2017-06-30 | Sage Therapeutics Inc | Compuestos neuroactivos y metodos de uso de los mismos. |
WO2016100940A1 (en) | 2014-12-19 | 2016-06-23 | The Broad Institute, Inc. | Dopamine d2 receptor ligands |
US10752588B2 (en) | 2014-12-19 | 2020-08-25 | The Broad Institute, Inc. | Dopamine D2 receptor ligands |
MA54851A (fr) | 2015-07-06 | 2021-12-08 | Sage Therapeutics Inc | Oxystérols et leurs procédés d'utilisation |
CA2991311A1 (en) * | 2015-07-06 | 2017-01-12 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
HUE053778T2 (hu) | 2015-07-06 | 2021-07-28 | Sage Therapeutics Inc | Oxiszterinek és ezek alkalmazása |
WO2017093354A1 (en) | 2015-11-30 | 2017-06-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Nmdar antagonists for the treatment of diseases associated with angiogenesis |
PT3436022T (pt) | 2016-04-01 | 2022-07-04 | Sage Therapeutics Inc | Oxisteróis e métodos de utilização dos mesmos |
US10752653B2 (en) | 2016-05-06 | 2020-08-25 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
EP3481846B1 (de) | 2016-07-07 | 2021-05-12 | Sage Therapeutics, Inc. | 11-substituierte 24-hydroxysterolverbindungen zur behandlung von krankheiten, die mit dem nmda-rezeptor verbunden sind |
BR112019006365A2 (pt) | 2016-09-30 | 2019-08-06 | Sage Therapeutics Inc | oxisteróis substituídos c7 e métodos de utilização dos mesmos |
EP3529257B1 (de) | 2016-10-18 | 2023-05-10 | Sage Therapeutics, Inc. | Oxysterole und verfahren zur verwendung davon |
JP2019532079A (ja) | 2016-10-18 | 2019-11-07 | セージ セラピューティクス, インコーポレイテッド | オキシステロールおよびその使用方法 |
WO2019071394A1 (zh) * | 2017-10-09 | 2019-04-18 | 华南农业大学 | 一种抗白色念珠菌的新型化合物及其制备方法和应用 |
US11981652B2 (en) | 2018-03-28 | 2024-05-14 | Emory University | GluN2C/D subunit selective antagonists of the N-methyl-D-aspartate receptor |
CN114539129B (zh) * | 2020-11-18 | 2023-06-09 | 上海中医药大学附属龙华医院 | 烯丙胺类双功能化合物及其用途 |
CA3230601A1 (en) * | 2021-09-02 | 2023-03-09 | Dennis Liotta | Glun2b-subunit selective antagonists of the n-methyl-d-aspartate receptors with enhanced potency at acidic ph |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2178412C2 (ru) * | 1996-07-19 | 2002-01-20 | Ф. Хоффманн-Ля Рош Аг | Производные 4-гидроксипиперидина |
US20040054013A1 (en) * | 2000-10-06 | 2004-03-18 | Kwok-Keung Tai | Nmda receptor channel blocker with neuroprotective activity |
US20060199864A1 (en) * | 2004-08-23 | 2006-09-07 | Traynelis Stephen F | Selection of pH-dependent compounds for in vivo therapy |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS54130587A (en) * | 1978-03-30 | 1979-10-09 | Otsuka Pharmaceut Co Ltd | Carbostyryl derivative |
DE2960178D1 (en) * | 1978-06-06 | 1981-04-09 | Hoechst Ag | New substituted phenylpiperazine derivatives, pharmaceutical compositions containing them and process for their preparation |
DE2824677A1 (de) * | 1978-06-06 | 1979-12-20 | Hoechst Ag | Neue substituierte phenylpiperazinderivate und verfahren zu deren herstellung |
JPS55162774A (en) * | 1979-06-06 | 1980-12-18 | Otsuka Pharmaceut Co Ltd | Carbostyril derivative |
JPS5646812A (en) * | 1979-09-27 | 1981-04-28 | Otsuka Pharmaceut Co Ltd | Central nervous system depressant |
JPS5649362A (en) * | 1979-09-28 | 1981-05-02 | Otsuka Pharmaceut Co Ltd | Thiocarbostyril derivative |
JPS5649361A (en) * | 1979-09-28 | 1981-05-02 | Otsuka Pharmaceut Co Ltd | Carbostyril derivative |
JPS579769A (en) * | 1980-06-23 | 1982-01-19 | Otsuka Pharmaceut Co Ltd | 2-benzimidazolinone derivative |
JPS58203968A (ja) * | 1982-05-21 | 1983-11-28 | Otsuka Pharmaceut Co Ltd | イソカルボスチリル誘導体 |
CN85108214A (zh) * | 1984-11-22 | 1986-08-20 | 赫彻斯特股份公司 | 新的取代的苯基哌嗪衍生物及其药物的制造方法 |
JPS62252783A (ja) * | 1986-02-13 | 1987-11-04 | ワ−ナ−−ランバ−ト・コンパニ− | ベンズ複素環式化合物 |
GB9005318D0 (en) * | 1990-03-09 | 1990-05-02 | Isis Innovation | Antiarrhythmic agents |
ZA9610745B (en) * | 1995-12-22 | 1997-06-24 | Warner Lambert Co | 4-Subsituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
CA2276373C (en) * | 1997-10-31 | 2010-01-12 | Suntory Limited | Arylpiperidinopropanol and arylpiperazinopropanol derivatives and pharmaceuticals containing the same |
IL145584A0 (en) * | 2000-10-02 | 2002-06-30 | Pfizer Prod Inc | Nmda nr2b antagonists for treatment |
US20040122090A1 (en) * | 2001-12-07 | 2004-06-24 | Lipton Stuart A. | Methods for treating neuropsychiatric disorders with nmda receptor antagonists |
US7375136B2 (en) * | 2001-03-08 | 2008-05-20 | Emory University | pH-dependent NMDA receptor antagonists |
DE10248925A1 (de) * | 2002-10-15 | 2004-04-29 | Proteosys Ag | Neue Verbindungen mit dopaminerger und/oder serotoninerger Aktivität |
JP2006528236A (ja) * | 2003-05-16 | 2006-12-14 | ファイザー・プロダクツ・インク | ジプラシドンを用いて認知を増強する方法 |
RS20050851A (sr) * | 2003-05-27 | 2008-04-04 | Forest Laboratories Inc., | Kombinacija antagonista nmda receptora i selektivnog inhibitora ponovnog preuzimanja serotonina za lečenje depresije i drugih poremećaja raspoloženja |
HUP0401526A2 (en) * | 2004-07-29 | 2006-04-28 | Richter Gedeon Vegyeszet | Aryloxy acetic acid amide derivatives, pharmaceutical compositions comprising thereof, methods for their preparation and their use |
WO2007006738A2 (en) * | 2005-07-12 | 2007-01-18 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition comprising 2 , 3-disubstituted tropanes for the treatment of disorders of sexual desire |
TWI329641B (en) * | 2005-08-31 | 2010-09-01 | Otsuka Pharma Co Ltd | (benzo[b]thiophen-4-yl)piperazine compounds, pharmaceutical compositions comprising the same, uses of the same and processes for preparing the same |
JPWO2007099828A1 (ja) * | 2006-02-23 | 2009-07-16 | 塩野義製薬株式会社 | 環式基で置換された含窒素複素環誘導体 |
WO2008020306A2 (en) * | 2006-08-18 | 2008-02-21 | Pfizer Products Inc. | Isoindole derivatives |
AU2008272964A1 (en) * | 2007-06-29 | 2009-01-08 | Emory University | NMDA receptor antagonists for neuroprotection |
-
2009
- 2009-05-11 CA CA2722776A patent/CA2722776A1/en not_active Abandoned
- 2009-05-11 JP JP2011508724A patent/JP2011520815A/ja active Pending
- 2009-05-11 KR KR1020107025739A patent/KR20110016891A/ko not_active Application Discontinuation
- 2009-05-11 SG SG2013077359A patent/SG195568A1/en unknown
- 2009-05-11 CN CN2009801184245A patent/CN102762207A/zh active Pending
- 2009-05-11 MX MX2010012186A patent/MX2010012186A/es not_active Application Discontinuation
- 2009-05-11 WO PCT/US2009/043502 patent/WO2009137843A2/en active Application Filing
- 2009-05-11 AU AU2009244082A patent/AU2009244082A1/en not_active Abandoned
- 2009-05-11 EA EA201071291A patent/EA020339B1/ru not_active IP Right Cessation
- 2009-05-11 BR BRPI0912362A patent/BRPI0912362A2/pt not_active IP Right Cessation
- 2009-05-11 EP EP09743829.5A patent/EP2296658A4/de not_active Withdrawn
- 2009-05-11 NZ NZ589764A patent/NZ589764A/xx not_active IP Right Cessation
-
2010
- 2010-10-24 IL IL208895A patent/IL208895A0/en unknown
- 2010-11-02 US US12/938,138 patent/US20110160223A1/en not_active Abandoned
- 2010-11-05 ZA ZA2010/07958A patent/ZA201007958B/en unknown
- 2010-11-16 CO CO10143058A patent/CO6341558A2/es not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2178412C2 (ru) * | 1996-07-19 | 2002-01-20 | Ф. Хоффманн-Ля Рош Аг | Производные 4-гидроксипиперидина |
US20040054013A1 (en) * | 2000-10-06 | 2004-03-18 | Kwok-Keung Tai | Nmda receptor channel blocker with neuroprotective activity |
US20060199864A1 (en) * | 2004-08-23 | 2006-09-07 | Traynelis Stephen F | Selection of pH-dependent compounds for in vivo therapy |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11865088B2 (en) | 2018-10-05 | 2024-01-09 | Clexio Biosciences Ltd. | Method of treating major depressive disorder |
US11957645B2 (en) | 2018-10-05 | 2024-04-16 | Clexio Biosciences Ltd. | Method of treating major depressive disorder |
US12016832B2 (en) | 2018-10-05 | 2024-06-25 | Clexio Biosciences Ltd. | Method of treating major depressive disorder |
Also Published As
Publication number | Publication date |
---|---|
EA201071291A2 (ru) | 2011-04-29 |
ZA201007958B (en) | 2011-07-27 |
EP2296658A2 (de) | 2011-03-23 |
MX2010012186A (es) | 2011-02-22 |
CA2722776A1 (en) | 2009-11-12 |
BRPI0912362A2 (pt) | 2015-10-06 |
CO6341558A2 (es) | 2011-11-21 |
AU2009244082A1 (en) | 2009-11-12 |
EP2296658A4 (de) | 2014-01-15 |
KR20110016891A (ko) | 2011-02-18 |
NZ589764A (en) | 2012-10-26 |
EA201071291A3 (ru) | 2014-02-28 |
WO2009137843A9 (en) | 2010-03-11 |
IL208895A0 (en) | 2011-01-31 |
CN102762207A (zh) | 2012-10-31 |
US20110160223A1 (en) | 2011-06-30 |
WO2009137843A2 (en) | 2009-11-12 |
SG195568A1 (en) | 2013-12-30 |
JP2011520815A (ja) | 2011-07-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EA020339B1 (ru) | Nmda рецепторные антагонисты для лечения нейропсихиатрических расстройств | |
AU4806697A (en) | Compositions and methods for reducing respiratory depression and attendant side effects of mu opioid compounds | |
WO2007093624A2 (en) | Pharmaceutical compositions for the treatment of attention deficit hyperactivity disorder comprising flibanserin | |
EP1641461A1 (de) | KOMBINATIONSPRODUKT MIT EINEM ANTAGONISTEN ODER INVERSEN AGONISTEN VON HISTAMINE-REZEPTOR H&lt;SB&gt;3&lt;/SB&gt; UND EINEM ANTIPSYCHOTISCHEN ODER ANTIDEPRESSIVEN MITTEL, UND IHRE VERWENDUNG ZUR HERSTELLUNG EINES MEDIKAMENTS ZUR VERHINDERUNG DER NACHTEILIGEN WIRKUNGEN VON PSYCHOTROPIKA | |
US20230098667A1 (en) | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment | |
US7030124B2 (en) | Method of treating depression with delta receptor agonist compounds | |
MX2007012070A (es) | Tratamiento de la epilepsia con ligandos del receptor h3 de histamina, tipo alquilaminas no imidazol. | |
WO2009146031A1 (en) | Methods of treating disease-induced ataxia and non-ataxic imbalance | |
AU2018264030A1 (en) | Treatment regimens | |
KR20180037975A (ko) | 포도막 흑색종을 치료하기 위한 mdm2 억제제 | |
US20010047016A1 (en) | Method for treating depression | |
US20140148432A1 (en) | Compounds for the Treatment of Neurological Disorders | |
US20050038083A1 (en) | Combination of phenylcarboxamides with blockers of the IKr channel and their use for the treatment of atrial arrhythmias | |
JP2021119192A (ja) | 医薬組成物 | |
SK7062001A3 (en) | Remedial agent for erectile dysfunction | |
JP7514534B2 (ja) | 認知障害を処置するためのベンゾジアゼピン誘導体、組成物および方法 | |
US20240132513A1 (en) | Benzazepine derivatives, compositions, and methods for treating cognitive impairment | |
EP3424506B1 (de) | Pharmazeutische zusammensetzung zur behandlung von funktionalen psychiatrischen störungen | |
EP1105132B1 (de) | Die verwendung von r (+)- g(a)-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol zur behandlung von obstruktive schlafapnoe | |
WO2023133135A2 (en) | Small molecule adrenoreceptor antagonists and uses thereof | |
AU2013203941A1 (en) | NMDA receptor antagonists for the treatment of neuropsychiatric disorders | |
WO2018197638A1 (en) | Novel use of (5r)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-d-prolinamide | |
JP2007522175A (ja) | 社会恐怖症の治療用の2−メトキシ−5−(5−トリフルオロメチル−テトラゾール−1−イル−ベンジル)−2s−フェニル−ピペリジン−3s−イル)アミン |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM RU |